Effects of estrogen replacement therapy on natriuretic peptides and blood pressure

OBJECTIVE: Estrogen replacement therapy (ERT) has been reported to affect blood pressure. Since natriuretic peptides have natriuretic and vasodilatory activity and also inhibit the renin-angiotensin-aldosterone system and lower blood pressure, it was hypothesized that the changes in blood pressure effected by ERT might be mediated via changes in natriuretic peptides. METHODS: Fifty-eight postmenopausal hysterectomized women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate 2 mg/day or transdermal estradiol gel containing 1 mg estradiol/day for 6 months. Blood pressure was measured by using an automatic, oscillometric device. Plasma atrial natriuretic peptide (ANP), N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP), aldosterone, and renin were determined by radioimmunoassay. RESULTS: The mean decrease in diastolic blood pressure was -6 mmHg both in the peroral group (n = 26) (P = 0.002) and in the gel group (n = 27) (P = 0.001), and the corresponding decreases in systolic blood pressure were -4 mmHg (P = 0.070) and -7 mmHg (P = 0.028) in the sitting position. Plasma NT-proANP rose from 212 to 264 pmol/l (P = 0.001) on peroral ERT and from 240 to 292 pmol/l (P = 0.008) on transdermal ERT. No significant changes were observed in the plasma ANP, BNP, aldosterone, and renin levels. CONCLUSIONS: Both peroral and transdermal ERT result in elevated plasma levels of NT-proANP, indicating an activation of the natriuretic peptide system. This could explain, at least in part, the lowering of blood pressure during ERT.     

Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women

Objectives: The aim of this study was evaluation of the influence of hormonal replacement therapy (HRT) on the regional cerebral blood flow in postmenopausal women. Methods: The study group were 20 postmenopausal women, mean age 48.7 years (S.D. ±4.9 years). The control group were ten regularly menstruating women, mean age 32.6 years (S.D. ±13.2 years). In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17β-estradiol level with the use of radioimmunological method. Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography (SPECT). Tracer accumulation evaluation was performed in three slices defined as: cerebellar slice, thalamic slice and ventricular slice, the reference region was delineated in the cerebellum. In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT. Results: Before HRT mean value of the Kupperman index in the study group was 29.8 points (S.D. ±7.1 points); 17β-estradiol 27 pg/ml (S.D. ±2 pg/ml); FSH 56 IU/l (S.D. ±49.5 IU/l); SPECT study revealed cerebral blood flow impairment in ten women. In all the studied slices cerebral blood flow was lower in the study group than in the controls. After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points (S.D. ±2.1 points) (P<0.05); 17β-estradiol 44 pg/ml (S.D. ±25 pg/ml); FSH 36.4 IU/l (S.D. ±57.3 ng/ml); we found cerebral blood flow increase in all studied slices: right cerebellar slice: 5.2%; left cerebellar slice: 4.1%; right thalamic slice: 3.8%; left thalamic slice: 3.3%; right ventricular slice: 7.5%*; left ventricular slice: 6.7%* (* P<0.05). Conclusions: Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women. HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17β-estradiol level.     

Differential age effects on cerebral blood flow and BOLD response to encoding: associations with cognition and stroke risk

Changes in the cerebrovascular system due to age or disease can significantly alter the blood-oxygenation-level-dependent (BOLD) signal and complicate its interpretation. The simultaneous acquisition of arterial spin labeling (ASL) and BOLD data represents a useful technique to more fully characterize the neurovascular underpinnings of functional brain response to cognition. We conducted a functional magnetic resonance imaging (FMRI) study of episodic memory encoding to investigate whether age is related to cerebral blood flow (CBF) and BOLD response in the medial temporal lobe (MTL). Results demonstrated a significant reduction in resting-state CBF in older compared to young adults. Conversely, older adults showed significantly increased CBF but not BOLD response in the MTL during picture encoding relative to young adults. Correlations between CBF response and cognition were demonstrated whereas associations with BOLD were not observed. Stroke risk was associated with both CBF and BOLD response. Results suggest that aging effects on CBF and BOLD responses to encoding are dissociable and that cerebrovascular alterations contribute to findings of age-related differences.     

Critical appraisal of effects of estrogen replacement therapy on symptoms of depressed mood

That estrogen plays a role in the regulation of mood has been postulated since extracts of animal ovarian tissue were administered to oophorectomized women at the end of the last century to alleviate psychological symptoms thought to be related to the removal of the ovaries. The occurrence of depressive symptoms in the perimenopause is associated with a variety of factors. A previous history of either depression and/or premenstrual syndrome as well as cognitive factors explain most of the variance. There are no consistent findings of a correlation between any serum hormone level and severity or presence of mood symptoms. Neurobiological studies show, with regard to an antidepressant effect, promising effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic and GABAergic functions. Progestogens seem to oppose some of these effects. The role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials showed a modest effect on symptoms of depression. However, the predominantly poor methodological quality does not allow generalisation and recommendations. A "tonic" effect on well-being in non- or mild depressed women should not be regarded as true antidepressant effect. Results yielded in studies of surgically menopausal women may not be applicable to women with natural menopause. There is a great potential for exploring various types, doses, and routes of administration of both antidepressants and sex hormones. With regard to the domino theory, future studies should also focus on the mediation of treatment effects through alleviation of vasomotor symptoms or sleep quality.     

Lymphangioleiomyomatosis in a menopausal woman on estrogen replacement therapy

The case of lymphangioleiomyomatosis (LAM) was presented. Woman (55 years) receiving for several years estrogens with the symptoms of disease (dyspnea, nonproductive cough, chylous pleural fluid) appeared after menopause. Suggestive clinical symptoms and chest HRCT scan confirmed clinical diagnosis of LAM. Two years after discontinuation of estrogen medication her clinical condition and radiological picture of lungs improved.     

Longitudinal changes in regional cerebral blood flow in a normal elderly group.

Only one published study to date has examined longitudinal age-changes in regional cerebral blood flow (rCBF) in an elderly group. It found rCBF declined significantly in their elderly sample over a 24 to 42 month period. The current study attempts to cross-validate the earlier study's findings with an older normal elderly group and a longer time interval between rCBF studies. This study is consistent with that investigation. The normal elderly did exhibit significant declines in blood flow across a variety of indices including: gray and white matter and the Initial Slope Index. These declines were generally on the order of.50 to.75 of a standard deviation loss. No significant differences in blood flow decline between males and females were discerned. While the young-old did exhibit greater blood flow than the old-old there were no significant differences in the rate of decline between the two age-groups.     

Influence of estrogen replacement therapy on plasma lipid peroxidation.

OBJECTIVE: To observe whether any relationship exists between the concentration of plasma estradiol (E2) and the plasma concentrations of malondialdehyde (MDA) or whether a relationship exists between the concentration of plasma E2 and the activity of the erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in ovariectomized female Wistar rats (treated and untreated with E2). DESIGN: We used 40 ovariectomized Wistar rats randomly assigned to four groups. The first group was allowed to evolve freely with no treatment. A gel containing 17beta-estradiol was administered transdermally to the other three groups at doses of 4, 8, and 16 microg/day, respectively. After 15 days of treatment, blood samples were obtained from the four groups. The concentrations of plasma MDA and E2 and the activities of erythrocyte catalase and SOD were determined. RESULTS: There were significant correlations between the MDA levels and the logarithm (base 10) of the plasma E2 concentrations in both linear (p = 0.00093) and quadratic (p = 0.000001) regression analyses. No relationship was found between the E2 concentrations and the catalase and SOD activities. CONCLUSIONS: There was a clear relationship between the plasma levels of MDA and the logarithm of the plasma E2 concentrations, which was best demonstrated with a quadratic regression. This model may explain the contradictory findings presented by estrogens with respect to their pro-or antioxidant action.     

The effect of estrogen replacement therapy on cardiac autonomic regulation

OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.     

Sympathetic effects on cerebral and ocular blood flow in rabbits pretreated with indomethacin

The effects of unilateral stimulation of the cervical sympathetic chain on cerebral and ocular blood flow was investigated in 8 rabbits anesthetized with pentobarbital sodium and pretreated with indomethacin in order to inhibit the formation of prostaglandins. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta. Evans blue was given as a tracer for protein leakage during hypertension. Sympathetic stimulation had no significant effect on the blood flow in the brain under the two conditions studied. In the uvea marked effects of sympathetic stimulation were obtained at normotension as well as at hypertension. There were no indications of breakdown of the blood-brain barrier or the blood-aqueous barrier. Thus, there was no evidence for any prostaglandin-mediated inhibition of sympathetic effects in the brain or the eye.     

Early effects of cervical sympathetic stimulation on cerebral,ocular and cochlear blood flow

Autoregulatory mechanisms may be expected to modify effects of vasomotor nerve stimulation in many tissues. Attempts were made to reveal a distinct early, but transient effect of cervical sympathetic stimulation on cerebral, retinal and cochlear blood flow. The labelled microsphere method was used to determine regional blood flow during electrical stimulation of the cervical sympathetic chain for 15–25 s and 5 min. At a frequency of 6 Hz there was a 5% reduction in cerebral flow at 15–25 s and 7% at 5 min. In the choroid plexus the mean reduction was 22% at 15–25 s but decreased to 10% after 5 min. In the cerebellum, optic nerve and retina, sympathetic stimulation had no appreciable effect on the blood flow. In the cochlea and iris, the blood flow reductions were 25 and 32%, respectively, on both occasions. In the choroid, vasoconstriction increased with time, whereas in the masseter muscle there was a decrease. Thus in the present experiments no indication was found of an autoregulatory escape phenomenon in the brain, the eye or the cochlea. Some escape was noted in the masseter muscle.     

The effects of long-term ovariectomy and estrogen replacement therapy on learning and memory in monkeys (Macaca fascicularis)

This study determined the effects of estrogen loss and replacement therapy on learning and memory function in monkeys (Macaca fascicularis). The ability to learn, remember, and perform reversals of object discriminations and the accuracy on a spatial delayed response task were found to be comparable in young adult surgically menopausal monkeys receiving estrogen or placebo treatment for 5 or 16 months. Learning and memory abilities were comparable with baseline values following 2, 12, or 24 months of ovariectomy in monkeys. Pre- and postoperative injections of scopolamine in a subset of monkeys revealed only subtle increases in sensitivity on the delayed response task following ovariectomy. These observations in surgically menopausal monkeys have some parallels with those made in surgically menopausal women and suggest that, in the absence of other confounding factors, certain aspects of learning and memory may not be influenced by estrogen in primates.     

Gynecologic consequences of long-term, unopposed estrogen replacement therapy

We evaluated the gynecologic risks of unopposed, long-term estrogen use in postmenopausal women. Our medical record review showed that unopposed estrogen users (mean dose, 0.9 mg of conjugated estrogens) had a significantly higher (P < 0.001) incidence of abnormal vaginal bleeding, curettage, hysterectomy, and endometrial cancer. The ratios of occurrence of these events among users compared with non-users were 7.8, 4.9, 6.6 and 7.7. The prevalence of hysterectomy reached 28.2% of users compared with 5.3% of non-users, and endometrial carcinoma developed in 9.9% of users compared with 1.4% of non-users.     

Correlation between cerebral blood volume and cerebral blood flow in the cat

Summary Blood flow and blood volume were measured simultaneously in the same cerebral region in anaesthetized cats with controlled respiration. The measurements were made with the same scintillation-detector, using the freely diffusible indicator ¹³³ Xenon for flow determinations and the intra-vascular indicator RISA (¹³¹I) for volume recordings. A very high correlation was found between volume and flow changes (r = .96, p < 0.001). This finding indicates that variations of regional cerebral blood volume are accompanied by proportional blood flow changes.Attaché de recherche au C.N.R.S., Laboratoire de Neurophysiologie, Hopital Henri Rouselle, Paris, France.     

Effect of neurotropin on regional cerebral blood flow and systemic blood pressure

Experiments on rabbits show that neurotropin has no effect on regional cerebral flow and systemic blood pressure under normal conditions, but reduces regional cerebral flow in partial circulatory hypoxia (ischemia) and recirculation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 612–614, June, 1998     

大鼠脑缺血及再灌流对脑组织血流量、ATP和乳酸水平含量的影响

目的和方法：本研究采用大鼠可逆性阻塞大脑中动脉所致的局灶性脑缺血再灌流模型，观察缺血３ｈ再灌流３ｈ、缺血６ｈ再灌流３ｈ对脑组织脑局部血流量（ｒｅｇｉｏｎａｌｃｅｒｅｂｒａｌｂｌｏｏｄｆｌｏｗ，ｒＣＢＦ）、ＡＴＰ、乳酸及脑水含量的影响。结果：缺血３ｈｒＣＢＦ明显下降（Ｐ＜００１），再灌流３ｈ升至缺血前６５３％（Ｐ＜００１）。缺血３ｈ再灌流３ｈ与缺血６ｈ组比较，ＡＴＰ明显恢复（Ｐ＜００１），乳酸含量明显下降（Ｐ＜００１），脑水含量明显减少（Ｐ＜００５）。缺血６ｈ再灌流３ｈ与缺血９ｈ组比较，尽管ＡＴＰ明显恢复（Ｐ＜００１），乳酸含量下降（Ｐ＜００１），但脑水含量无显著差异（Ｐ＞０１）。结论：缺血３ｈ再灌流３ｈ保护“半暗带”的效果优于缺血６ｈ再灌流３ｈ。